Nucleostemin is indispensable for the maintenance and genetic stability of hematopoietic stem cells |
| |
Authors: | Masayuki Yamashita Eriko Nitta Go Nagamatsu Yoshiko Matsumoto Ikushima Kentaro Hosokawa Fumio Arai Toshio Suda |
| |
Institution: | 1. Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan;2. Research Fellow of the Japan Society for the Promotion of Science, Kojimachi Business Center Building, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan |
| |
Abstract: | Nucleostemin is a nucleolar protein known to play a variety of roles in cell-cycle progression, apoptosis inhibition, and DNA damage protection in embryonic stem cells and tissue stem cells. However, the role of nucleostemin in hematopoietic stem cells (HSCs) is yet to be determined. Here, we identified an indispensable role of nucleostemin in mouse HSCs. Depletion of nucleostemin using short hairpin RNA strikingly impaired the self-renewal activity of HSCs both in vitro and in vivo. Consistently, nucleostemin depletion triggered apoptosis rather than cell-cycle arrest in HSCs. Furthermore, DNA damage accumulated during cultivation upon depletion of nucleostemin. The impaired self-renewal activity of HSCs induced by nucleostemin depletion was partially rescued by p53 deficiency but not by p16Ink4a or p19Arf deficiency. Taken together, our study demonstrates that nucleostemin protects HSCs from DNA damage accumulation and is required for the maintenance of HSCs. |
| |
Keywords: | Nucleostemin Hematopoietic stem cells Apoptosis DNA damage |
本文献已被 ScienceDirect 等数据库收录! |
|